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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2005

N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration.

Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.

Adult↗

PubMed2005

Interstitial white matter neuron density in the dorsolateral prefrontal cortex and parahippocampal gyrus in schizophrenia.

Alterations in the density or distribution of interstitial white matter neurons are taken as evidence in support of an early developmental component to schizophrenia. However, the existence and nature of interstitial white matter neuron changes in schizophrenia remain inconclusive. Recently, we reported that interstitial white matter neuron density is increased in the superficial white matter of the superior temporal gyrus in schizophrenia, but unchanged in deep white matter. This study extends our investigations to the dorsolateral prefrontal cortex and parahippocampal gyrus. Using the specific neuronal antibody NeuN, interstitial white matter neuron density was found to be increased in schizophrenia in the superficial white matter of the dorsolateral prefrontal cortex, with no significant changes elsewhere. As interstitial white matter neurons are presumed to be remnants of the embryonic cortical subplate, these findings provide additional evidence supportive of an early developmental abnormality in schizophrenia.

Adult↗

PubMed2001

N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia.

OBJECTIVE: The N-methyl-D-aspartic acid (NMDA) class of glutamate receptors has received attention in the pathophysiology of schizophrenia because of the similarity between some schizophrenic symptoms and symptoms caused by NMDA antagonists. To determine if NMDA receptor abnormalities were present at the mRNA level, expression of NMDA receptor (NR) subunits NR(1), NR(2A), and NR(2B) was measured in specimens from the dorsolateral prefrontal cortex and the occipital cortex of elderly patients with schizophrenia and normal elderly subjects. METHOD: Postmortem specimens from antemortem assessed and diagnosed elderly patients with schizophrenia (N=26) were compared with those from a neuropathologically and neuropsychiatrically normal elderly comparison group (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of the NR(1), NR(2A), and NR(2B) subunits and of postsynaptic density 95 (PSD-95), a protein associated with postsynaptic NMDA receptors, was studied with quantitative real-time reverse transcriptase polymerase chain reaction. RESULTS: Expression of NR(1) and NR(2A) but not NR(2B) subunits was higher in the dorsolateral prefrontal cortex and the occipital cortex of patients with schizophrenia than in the normal and Alzheimer's disease groups. In contrast, NR(1) expression was significantly lower in the Alzheimer's disease group. Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects and correlated strongly with the expression of NR(2A) and NR(2B) in both cortical regions and with expression of NR(1) in the occipital cortex. These results were not influenced by neuroleptic exposure history, postmortem interval, or age of the subject. CONCLUSIONS: NMDA receptor subunits are abnormally expressed in elderly patients with schizophrenia. The disproportionate expression of the NR(1) and NR(2A) subunits relative to NR(2B) expression may have implications for the pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to glutamate and glutamatergic drugs.

Actins↗

PubMed2006

Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson's disease.

OBJECTIVE: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) is effective in the treatment of depression in patients with Parkinson disease (PD). However, since research into the effect of this type of rTMS regime on motor function is limited, we studied the effect of rTMS over the DLPFC on the motor functions in PD patients. METHODS: Thirteen patients were randomly assigned into 2 groups, one receiving real-rTMS (90% of resting motor threshold, 10 Hz, 450 pulses-day for 10 consecutive days) over the DLPFC contralateral to the more affected side, and the other group receiving sham-rTMS. Assessment included a clinical motor evaluation using part III of the Unified Parkinson's Disease Rating Scale (UPDRS), and several motor tasks. The UPDRS was applied before and after 10 days of rTMS. Finger tapping, reach movement, grip movement and gait were measured in each session before and after the rTMS over the 10 day period. RESULTS: Statistical analysis (ANOVA for repeated measures; group *day *side *rTMS) only showed a significant effect for finger tapping, reach movement and gait for the factor day. No significant change was reported for the UPDRS in any group. CONCLUSIONS: Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status, and the improvement in performance of motor tasks can be attributed to the effects of practice. SIGNIFICANCE: rTMS over the DLPFC did not lead to any motor improvement in PD patients.

Aged↗

PubMed1999

The left dorsolateral prefrontal cortex and random generation of responses: studies with transcranial magnetic stimulation.

Evidence from PET studies suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in generation of random responses. We used TMS to examine the specific role of this area in random generation of responses, a task which requires holding information 'on line', suppression of habitual or stereotyped response patterns, intrinsic response generation, monitoring of responses and modification of production strategies. From the results of a previous study of the effects of TMS on random number generation, we proposed a network modulation model, whereby suppression of habitual responses is considered a key process of random response generation and is achieved through the modulatory influence of the left DLPFC over an associative network distributed in the superior temporal cortex. The aim of the present study was to further investigate the generality of this model by examining the effects of short trains of TMS over the left or right DLPFC or medial frontal cortex on random letter generation in healthy participants. TMS over the left DLPFC significantly increased non-randomness relative to control no stimulation trials, which was not obtained with TMS over the right DLPFC or medial frontal cortex. The results suggest the generality of network modulation model of random response generation.

Adult↗

PubMed2006

Acute changes in frontoparietal activity after repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex in a cued reaction time task.

Lesion and functional imaging studies in humans have suggested that the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and intraparietal sulcus (IPS) are involved in orienting attention. A functional magnetic resonance imaging study supplemented by a behavioral experiment examined the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) conditioning to the right and left DLPFC on reaction times and synaptic activity as indexed by changes in the blood oxygenation level-dependent (BOLD) signal during a cued choice reaction time task. Orienting precues were either correct (valid) or incorrect (invalid) with respect to the subsequent move cue. The effects of real and sham rTMS were compared for each site of stimulation. Invalid trials showed a significant increase in response times and increases in the BOLD signal in right frontal and parietal regions when compared with valid trials. Conditioning left DLPFC with rTMS led to decreased BOLD signal during performance of this reorienting task in areas including left VLPFC and left IPS. Comparing invalid to valid trials after right DLPFC conditioning revealed decreased BOLD signal in right VLPFC. Data from the behavioral study showed that right DLPFC rTMS selectively increases response times in invalid trials. This effect was only present in the first 10 min after rTMS conditioning. No effect was found in either validly or invalidly cued trials with left DLPFC conditioning. These results suggest that 5 Hz rTMS over right DLPFC exerts remote effects on the activity of areas that functionally interact with the DLPFC during attentional processes, particularly when the reorienting of attention is more demanding as in invalid trials.

Adult↗

PubMed2004

Area-selective neuronal activity in the dorsolateral prefrontal cortex for information retrieval and action planning.

We compared how neurons in the dorsal and ventral regions of the dorsolateral prefrontal cortex (dl-PFC) participate in processing 2 sets of sensory signals, given at intervals, to generate plans for future actions. For the first set of visual signals, neurons in the ventral region of dl-PFC responded preferentially to the visuospatial properties of the signal, whereas neurons in the dorsal region of dl-PFC were involved primarily in retrieving information from the signal, such as the location of the target or which arm to use. For the second set of visual signals, most ventral dl-PFC neurons reflected either the sensory properties of the signals or the information retrieved from each signal. By contrast, dorsal neurons were involved more in integrating information about the target location and which arm to use to reach the target, thereby generating information that could be used to plan future actions. Thus sensorimotor transformations in the dorsolateral PFC appear to be time-variant and region-selective.

Animals↗

PubMed1978

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys.

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, reinforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.

Animals↗

PubMed2001

Ethanol reduces rCFB activation of left dorsolateral prefrontal cortex during a verbal fluency task.

In a previous study in normal subjects (Wendt et al., 1994), using a reversing checkerboard as activation stimulus, we found that the coupling between local neuronal activity and regional cerebral blood flow was preserved following ethanol, and that a right-sided occipital activation response seen during sobriety became symmetrical during inebriation. In the present study we investigated if ethanol has a detrimental effect also on the activation of the left dorsolateral prefrontal cortex found in normals during verbal fluency. Measurements of regional cerebral blood flow in 20 healthy, young, male, right-handed volunteers during rest and verbal fluency were made during sobriety and inebriation (0.06% blood alcohol concentration) with a 1-week interval. We found a decrease in word production during inebriation. The normal activation within the frontotemporal part of the left dorsolateral prefrontal cortext was preserved during inebriation. The activation of this region seems thus to be robust to the effects of ethanol. During inebriation no activation response to the word fluency test was found in the anterior prefrontal part of the dorsolateral prefrontal cortex. This region is important for working, temporal, and short-term memory functions, processes that are affected by ethanol. Hemispheric functioning and specialization seem to be adversely affected by ethanol, regardless of which hemisphere is most involved while sober.

Adult↗

PubMed2000

Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.

BACKGROUND: Working memory (WM) deficits in schizophrenia have been associated with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies. We previously found increased DLPFC activation in schizophrenic versus normal subjects during WM performance (Manoach et al 1999b). We now have investigated whether schizophrenic subjects recruit different brain regions, particularly the basal ganglia and thalamus, components of frontostriatal circuitry thought to mediate WM. METHODS: We examined regional brain activation in nine normal and nine schizophrenic subjects during WM performance using functional magnetic resonance imaging. Subjects performed a modified version of the Sternberg Item Recognition Paradigm that included a monetary reward for correct responses. We compared high and low WM load conditions to each other and to a non-WM baseline condition. We examined activation in both individual subjects and averaged group data. RESULTS: Relative to normal subjects, schizophrenic subjects exhibited deficient WM performance, at least an equal magnitude of right DLPFC activation, significantly greater left DLPFC activation, and increased spatial heterogeneity of DLPFC activation. Furthermore, only the schizophrenic group activated the basal ganglia and thalamus, even when matched for task performance with the normal group. CONCLUSIONS: Aberrant WM performance and brain activation in schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves WM. Future studies will elucidate the contribution of the anatomical components of this circuitry to WM deficits.

Adult↗

PubMed1999

Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns.

The cytoarchitecture of the human and the macaque monkey dorsolateral prefrontal cortex has been examined in a strictly comparative manner in order to resolve major discrepancies between the available segmentations of this cortical region in the human and the monkey brain. In addition, the connections of the dorsolateral prefrontal cortical areas were re-examined in the monkey. The present analysis showed that only a restricted portion of what had previously been labelled as area 46 in the monkey has the same characteristics as area 46 of the human brain; the remaining part of this monkey region has the characteristics of a portion of the middle frontal gyrus in the human brain that had previously been included as part of area 9. We have labelled this cortical area as 9/46 in both species. These two areas (i.e. 46 and 9/46), which constitute the lower half of the mid-dorsolateral frontal cortex, have a well-developed granular layer IV, and can easily be distinguished from area 9, on the upper part of the mid-dorsolateral region, which does not have a well-developed granular layer IV. Area 9 has the same basic pattern of connections as areas 46 and 9/46, but, unlike the latter areas, it does not receive input from the lateral parietal cortex. Caudal to area 9, on the dorsomedial portion of the frontal cortex, there is a distinct strip of cortex (area 8B) which, unlike area 9, receives significant input from the prestriate cortex and the medial parietal cortex. The present results provide a basis for a closer integration of findings from functional neuroimaging studies in human subjects with experimental work in the monkey.

Animals↗

PubMed2003

Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia.

OBJECTIVE: The identification of neurobiological intermediate phenotypes may hasten the search for susceptibility genes in complex psychiatric disorders such as schizophrenia. Earlier family studies have suggested that deficits in executive cognition and working memory may be related to genetic susceptibility for schizophrenia, but the biological basis for this behavioral phenotype has not been identified. METHOD: The authors used functional magnetic resonance imaging (fMRI) during performance of the N-back working memory task to assess working memory-related cortical physiology in nonschizophrenic, cognitively intact siblings of patients with schizophrenia. They compared 23 unaffected siblings of schizophrenic patients to 18 matched comparison subjects. As a planned replication, they studied another 25 unaffected siblings and 15 comparison subjects. RESULTS: In both cohorts, there were no group differences in working memory performance. Nevertheless, both groups of siblings showed an exaggerated physiological response in the right dorsolateral prefrontal cortex that was qualitatively similar to results of earlier fMRI studies of patients with schizophrenia. CONCLUSIONS: These fMRI data provide direct evidence of a primary physiological abnormality in dorsolateral prefrontal cortex function in individuals at greater genetic risk for schizophrenia, even in the absence of a manifest cognitive abnormality. This exaggerated fMRI response implicates inefficient processing of memory information at the level of intrinsic prefrontal circuitry, similar to earlier findings in patients with schizophrenia. These data predict that inheritance of alleles that contribute to inefficient prefrontal information processing will increase risk for schizophrenia.

Adult↗

PubMed2005

Information processing flow and neural activations in the dorsolateral prefrontal cortex in the Stroop task in schizophrenic patients. A spatially filtered MEG analysis with high temporal and spatial resolution.

Using a spatially filtered magnetoencephalography analysis (synthetic aperture magnetometry), we estimated neural activations in the Stroop task in nearly real time for schizophrenic patients with/without auditory hallucinations and for normal control subjects. In addition, auditory hallucinations were examined through the information processing flow of the brain neural network, including the frontal regions. One hundred unaveraged magnetoencephalography signals during the incongruent stimulus responses were analyzed with a time window of 200 ms in steps of 50 ms. In the 25-60-Hz band, cortical regions that showed significant current source density changes were examined for each time window. The three groups showed significantly decreased current source density, corresponding to neural activation, with temporal overlap along the fundamental cognitive information processing flow: sensory input system, executive control system, motor output system. Transient neural activations in the dorsolateral prefrontal cortex were bilateral with left-side dominancy for normal controls, left-lateralized for nonhallucinators and right-lateralized for hallucinators. Our results suggest that the dysfunction in the left dorsolateral prefrontal cortex was related to auditory hallucinations, while the information processing flow was unaffected in the schizophrenic subjects in the Stroop task.

Adolescent↗

PubMed1999

Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI.

BACKGROUND: Neuroimaging studies of schizophrenic subjects performing working memory (WM) tasks have demonstrated a relative hypoactivity of prefrontal cortex compared with normal subjects. METHODS: Using functional magnetic resonance imaging (fMRI), we compared dorsolateral prefrontal cortex (DLPFC) activation in 12 schizophrenic and 10 normal subjects during rewarded performance of a WM task. Subjects performed a modified version of the Sternberg Item Recognition Paradigm (SIRP), a continuous performance, choice reaction time (RT) task that requires WM. We compared a high WM load condition with a nonWM choice RT condition and with a low WM load condition. RESULTS: Schizophrenic subjects performed the tasks better than chance but worse than normal subjects. They showed greater activation than normal subjects in the left DLPFC but did not differ in the right DLPFC or in the control region. In the schizophrenic group, left DLPFC activation was inversely correlated with task performance, as measured by errors. CONCLUSIONS: These findings contrast with previous studies that demonstrated task-related hypofrontality in schizophrenia. Task parameters that may contribute to this difference are discussed. We hypothesize that the performance and activation differences we observed are also manifestations of prefrontal dysfunction in schizophrenia. They reflect inefficient functioning of the neural circuitry involved in WM.

Adult↗

PubMed2002

Comparative analysis of group II metabotropic glutamate receptor immunoreactivity in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects.

Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system, and a key neurotransmitter in prefrontal cortical function. Converging lines of evidence implicate prefrontal cortical dysfunction in the neurobiology of schizophrenia. Thus, aberrant glutamate neurotransmission may underlie schizophrenia and other complex disorders of behavior. Group II metabotropic receptors (mGluRs) are important modulators of glutamatergic and non-glutamatergic neurotransmission. Moreover, in an animal model, an agonist for group II mGluRs has been shown to reverse the behavioral, locomotor, and cognitive effects of the psychotomimetic drug phencyclidine. Accordingly, group II mGluRs constitute attractive targets for the pharmacotherapeutics and study of schizophrenia. Using immunocytochemistry and Western immunoblotting, we compared the localization and levels of group II mGluRs in Brodmann's area 46 of the dorsolateral prefrontal cortex from patients with schizophrenia and normal subjects. Consistent with previous reports, we found that immunolabeling of group II mGluRs is prominent in Brodmann's area 46. The majority of labeling was present on axon terminals distributed in a lamina-specific fashion. No apparent difference in the cellular localization or laminar distribution of immunoreactive group II mGluRs was noted between the two diagnostic groups. Similarly, the levels of receptor immunoreactivity determined by quantitative Western immunoblotting were comparable between schizophrenic patients and normal subjects. We conclude that while the function of group II mGluRs in Brodmann's area 46 of dorsolateral prefrontal cortex may be altered in patients with schizophrenia, this is not evident at the level of protein expression using an antibody against mGluR2 and mGluR3.

Adult↗

PubMed2005

Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia.

CONTEXT: It remains unclear whether altered regional brain physiological activity in patients with schizophrenia during working memory tasks relates to maintenance-related processes, manipulation-related (ie, executive) processes, or both. OBJECTIVE: To examine regional functional activations of the brain during maintenance- and manipulation-related working memory processing in patients with schizophrenia and in healthy comparison subjects. DESIGN: Functional images of the brain were acquired in 11 schizophrenic patients and 12 healthy control subjects (matched for age, sex, handedness, and parental education) during 2 spatial working memory paradigms, one contrasting maintenance-only processing with maintenance and manipulation processing and the other contrasting parametrically varying maintenance demands. RESULTS: Patients and controls showed activation of a large, spatially distributed network of cortical and subcortical regions during spatial working memory processing. When task demands required explicit manipulation of information held in memory, controls recruited right dorsolateral prefrontal cortex (Brodmann areas 45 and 46) to a significantly greater extent than patients. A similar effect was observed for the larger memory set sizes of the memory set size task. No other brain regions showed activation differences between groups for either task. These differences persisted when comparing activation maps for memory set sizes in which the 2 groups were equivalent in behavioral accuracy and when comparing subgroups of patients and controls matched for behavioral accuracy on either task. CONCLUSIONS: Physiological disturbances in the dorsolateral prefrontal cortex contribute differentially to patients' difficulties with maintaining spatial information across a brief delay, as well as with manipulating the maintained representation. These differences persisted when comparing conditions in which the 2 groups were equivalent in behavioral accuracy.

Adolescent↗

PubMed1989

Delayed response deficits produced by local injection of bicuculline into the dorsolateral prefrontal cortex in Japanese macaque monkeys.

Bicuculline (10-30 micrograms, but usually 30 micrograms) was injected locally into 20 different sites in the dorsolateral prefrontal cortex (PFC) of 2 Japanese macaque monkeys, while they were performing a delayed response task. The task was initiated by the rotation of a handle to a central zone by the wrist joint and consisted of seven periods: an initial waiting period of 0.3 s, a pre-cue period (central green lamp of 1.0 s), a cue period (left or right green cue of 0.3 s), a delay period of 4.0 s (occasionally 1 s), a go period (central red lamp; rotation of the handle to either the left or right zone within 1.0 s), a hold period (holding of the handle in either the left or the right zone), and a final reward period. The parameters of the task performance, such as the frequency of correct trials, the frequency of directional error trials in which the monkeys rotated the handle in an incorrect direction during the go period, and the frequency of omission error trials, in which the monkeys did not rotate the handle during the go period, were examined before and after the injection of bicuculline. The injections of bicuculline induced a burst of multi-neuronal activity around the sites of injection. Within 5 min of an injection into one of 7 different sites in the PFC, three different kinds of performance deficit were observed: 1) an increase in the frequency of error responses during the go period in both left-cue and right-cue trials, after injection into the dorso-caudal portion of the principal sulcus (2 sites); 2) an increase in the frequency of directional error responses during the go period in either left-cue or right-cue trials, after injection into the bottom of the middle principal sulcus (3 sites), and 3) an increase in the frequency of omission of responses during the go period, after injection into the dorsal region of the caudal principal sulcus (2 sites). Injections at the remaining 13 sites did not induce any deficits, although injections into the dorsal bank of the principal sulcus (3 sites) induced a decrease in the frequency of the task trials as a result of prolonged intertrial intervals (ITIs). Our results suggest that locally disturbed neuronal activity in different small areas of the PFC induces different deficits in the performance of the delayed response task.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Laminar distributions of neurons sensitive to acetylcholine, noradrenaline and dopamine in the dorsolateral prefrontal cortex of the monkey.

Sensitivities of neurons to acetylcholine (ACh), noradrenaline (NA) and dopamine (DA) were investigated at different depths of the dorsolateral prefrontal cortex (PFC) in awake or halothane-anesthetized macaque monkeys, using microiontophoretic techniques with multi-barreled electrodes. The laminar locations of tested neurons (n = 403) were estimated by reconstructing electrode tracks based on the microlesion made by passing a current through the recording barrel, which contained a carbon fiber. Iontophoretically applied drugs induced excitatory or inhibitory responses. Neurons excited by ACh (n = 105) were located mainly in layers III and V, and those inhibited by ACh (n = 126) were in layers III and IV. The majority of the NA-sensitive neurons (n = 123) were NA-inhibited neurons (n = 100), and were found most often in layers III and IV. The ratio of DA-sensitive neurons (excited, n = 74; inhibited, n = 63) to tested neurons was higher in the deep layers than in the superficial ones. These results indicate that sensitivities of the PFC neurons to ACh, NA and DA are not uniform between cortical layers, suggesting that each of these substances may predominantly influence the neuronal activity of particular layers of the monkey PFC.

Acetylcholine↗